Gift of Healing Cancer with "Nano" Approaches

“納米”抗癌療法

Student thesis: Doctoral Thesis

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Award date13 Aug 2018

Abstract

Cancer is one of the leading cause of mortality in this world today. Enormous attempts have been made to develop better methods for diagnosis and treatment of cancers. Other than tumour debulking, the present treatments mainly rely on chemotherapy and radiation therapy which also affect the healthy cells. Limitations of the current approaches indicate the emergency to develop personalized medicine to improve therapeutic methods to defend against this dreadful disease. In recent years, nanotechnology has provided unrivalled opportunities in the advancement of cancer research. The treatment method through imaging has the potential to change the current medical pattern of “see and treat”. Theransotics, which combine the diagnosis and therapy are expected to fulfill its role as precision medicine. In this thesis, I have demonstrated effective nanotheranostic agents and imaging agents which can effectively function as a nanomedicine for therapy and imaging of cancer.

Initially, Piperine nanoparticle has been prepared by adding piperine molecule and PEG (Pip NPs) which efficiently function as a nanotheranostic agent for cancer treatment by inducing both photo-enhanced chemotherapy and results in ferroptosis. Piperine is a bioactive alkaloid obtained from black pepper which has been used in traditional Chinese and Indian medicines. However, lack of water solubility and delivery system hindered their effective usage as a therapeutic drug. Herein, Pip NPs is prepared via a conventional reprecipitation method. The as prepared Pip NPs is used as a fluorescent probe for cellular imaging while functioning as an effective therapeutic drug. Fluorescent Pip NPs exhibit good water dispersibility, large stokes shift and excellent optical stability at different pH. It is observed that Pip NPs can produce singlet oxygen which results in cell death in HeLa cells. More importantly, Pip nanoparticle can inhibit cell death in the presence of iron chelator, liproxstatin-1 and it produces lipid reactive oxygen species. These observations indicate that Pip NPs may induce ferroptosis. Our work opens new perspectives for exploring novel nanotheranostic agents for biomedical applications.

Polymer dots (Pdots) have emerged as effective fluorescent probes for biomedical applications and attracted much interest due to their excellent optical properties and low cytotoxicity. In the second work, red-emitting P3HT (Poly (3-hexylthiophene-2, 5-diyl)) Pdot is demonstrated as a fluorescent probe for intracellular bioimaging. The as-prepared Pdot fluorescent probe exhibits good stability and has a large Stokes shift. Furthermore, it shows low cytotoxicity, broad absorption spectrum, resistance against photodegradation and good water dispersibility. These advantageous characteristics endow the P3HT Pdot as a promising fluorescent probe for bioimaging.